Novel synthetic analogs of sialyl Lewis X can inhibit angiogenesis in vitro and in vivo.

Selectins have been shown to play an important role in angiogenesis. We have set out to synthesize multiple analogs of the selectin ligand sialyl Lewis X. We show here that analogs of sialyl Lewis X at concentrations of 50 micrograms/ml or greater significantly inhibited angiogenesis in in vitro assays of endothelial cell migration and proliferation (p < 0.05). These analogs also exerted significant inhibitory effects in in vivo angiogenesis assays using the chick chorioallantoic membrane at doses of 2 mg/chick or greater (p < 0.05). In contrast, the related carbohydrate Lewis X did not inhibit angiogenesis in both in vitro and in vivo assays. These data indicate that angiogenesis can be inhibited specifically by synthetic analogs of sialyl Lewis X. These analogs may potentially be useful in the treatment of angiogenesis-related diseases.